The vnd/NK-2 homeodomain protein contains two regions in addition to the homeodomain that consist of amino acid sequences that have been highly conserved during evolution, which suggests that these regions of the protein are binding sites for molecules that are involved in vnd/NK-2 function. The two-hybrid system was used to screen a Drosophila cDNA expression library in yeast for cDNAs that encode proteins that interact with vnd/NK-2 homeodomain protein. Some of the cDNAs that were cloned correspond to the gene, no-ocelli (noc A), which encodes a zinc finger protein that is involved in axon guidance, synapse formation, and tracheal branching. noc A protein consists of a highly hydrophilic N-terminal region (amino acid residues 50-234) and a hydrophobic C-terminal region with 2 putative zinc finger motifs. In solution nocA was shown to form noc A-noc A homodimers with high affinity and noc A-NK-2 heterodimers with weaker affinity. The N-terminal region of the protein was shown to be necessary for both noc A-noc A and noc A-NK-2 interactions; whereas, the C-terminal region of the protein was required only for noc A-noc A dimer formation. Deletion of the C-terminal region of the protein decreased noc A-noc A homodimer formation about 10-fold and increased noc A-NK-2 heterodimer interaction about 3.5-fold.